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Quality of life in patients with primary hyperparathyroidism Expert Review of Pharmacoeconomics & Outcomes Research 2014.14:113-121. Downloaded from informahealthcare.com by Emory University on 04/19/15. For personal use only.

Expert Rev. Pharmacoecon. Outcomes Res. 14(1), 113–121 (2014)

Cristiana Cipriani*, Elisabetta Romagnoli, Mirella Cilli, Sara Piemonte, Jessica Pepe and Salvatore Minisola Department of Internal Medicine and Medical Disciplines, “Sapienza” University of Rome, Viale del Policlinico 155, 00161, Rome, Italy *Author for correspondence: Tel.: +39 064 997 2379 Fax: +39 064 470 4916 [email protected]

The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed through the unexpected finding of high serum calcium levels. However, though not yet considered as typical features of the disease and therefore not included in the guidelines for surgery, many data are available on neuropsycological manifestations and their impact on quality of life in asymptomatic patients. PHPT patients indeed show early experience nonspecific symptoms, such as weakness, depression, sleep disturbance, memory loss and anxiety. Although the underlining mechanisms have not been still identified, the prevalence of psychiatric and cognitive deficits has been investigated in many studies, as well as the possible association with quality of life and well-being improvement after surgery. This article aims to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings. KEYWORDS: asymptomatic . cognition . parathyroidectomy . primary hyperparathyroidism . psychological .

quality of life

Primary hyperparathyroidism (PHPT) is the third most frequent endocrine disorder, whose clinical manifestations involve many different organs. Besides the skeletal and renal disease, the classical PHPT was associated with both neurocognitive and psychiatric manifestations, as well as sleep disorders and suicidal ideation. The clinical picture of the disease has changed over the last 30 years, since the introduction of routine serum calcium determination. Hence, many asymptomatic patients are currently diagnosed with PHPT through the unexpected finding of high serum calcium levels. The 2008 guidelines for parathyroid surgery are based on the patient’s young age, serum calcium values or the presence of complications [1]. Among these, the classical skeletal and renal diseases associated with PHPT (i.e., low bone mineral density and/or fragility fractures and renal failure) are included in the guidelines [1]. Hence, the presence of a symptomatic disease is currently recognized as one of the primary indications for surgery. Conversely, therapeutic strategies in asymptomatic patients are still doubtful. On the other hand, a controversy could arise in the definition of

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10.1586/14737167.2014.873702

‘asymptomatic’ conditions. Indeed, in the last decade, there has been an increasing interest in the nonclassical manifestations of PHPT. Though not yet considered as typical features of the disease, and therefore, not included in the guidelines for surgery, many data are available in literature on several complications in asymptomatic patients [2–4]. In particular, many studies focused on neuropsychological symptoms, cognition and on quality of life [5–21]. In this regard, clinical practice commonly shows as many ‘asymptomatic’ PHPT patients report cognitive and neuropsychological symptoms. This article was aimed to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings. Quality of life in PHPT

Among the neuropsychological and cognitive symptoms associated with PHPT, depression, anxiety, weakness, easy fatigability, irritability, sleep disturbance, memory loss, personality changes, loss of initiative and concentration capacity are commonly observed. Studies on

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ISSN 1473-7167

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114

[14]

Parathyroidectomy group: significant improvement in bodily pain, general health, vitality, mental heath versus observation group

PHPT: Primary hyperparathyroidism; SF: ShortForm.

50 Ambrogini et al. (2007)

Asymptomatic PHPT

SF-36; Symptom checklist revised (SCL-90R)

[15]

Parathyroidectomy group: significant improvement in mental health and mental component summary score at 1 year Observation group: significant improvement in mental health at 2 year Only differences over time for the domain role emotional were in favor of surgery 119 (1-year data); 99 (2-year data) Bollerslev et al. (2007)

Asymptomatic PHPT

SF-36; Comprehensive Psychopathological Rating Scale

[10]

Parathyroidectomy group: significant improvement in social function, emotional role function, anxiety and phobia versus observation group; decline in physical function score Observation group: significant worsening in social functioning, physical problem, emotional problem, energy and health perception 53 Rao et al. (2004)

Mild asymptomatic PHPT

36-item SF health survey (SF-36); Symptom checklist revised (SCL-90R)

Ref. Result Patients (n)

Disease severity

Tools

Cipriani, Romagnoli, Cilli, Piemonte, Pepe & Minisola

Study (year)

Table 1. Neuropsychological manifestations in patients with primary hyperparathyroidism before and after parathyroid surgery: results from randomized controlled trials on parathyroidectomy versus observation.

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the field demonstrated a decline in both cognitive performance and mental status in PHPT patients versus control subjects [6–20]. In particular, memory tests for both immediate and delayed recall of contextually related material, spatial and working memory, nonverbal abstraction tests, as well as measures of verbal and visual learning and concentration have been assessed [5–20]. As far as the psychological assessment of PHPT patients, many data are available for investigating the presence, even subclinical, of depressive, anxiety or obsessive–compulsive symptoms, paranoid or suicidal ideation, somatization, aggression and psychoticism [5–18]. Finally, the possible impact of these neuropsychological symptoms on daily living has been evaluated through the quality of life assessment. Studies on quality of life in PHPT therefore focused on different components including the general health perception, bodily pain, physical and social functioning, vitality, emotional functions and mental health by means of validated scores [10,14]. The overall results of these studies seem to demonstrate that there is a significantly reduced quality of life in PHPT patients, as they scored significantly lower than age-matched controls in a great majority of the investigated domains [6–14]. A similar finding has also been observed in other metabolic bone diseases [21]. As far as the effect of surgery on cognitive and psychological functioning is concerned, as well as on the quality of life, available data to date still appear to be conflicting [6–20]. Indeed, prospective studies and randomized controlled trials comparing surgery and surveillance in patients with mild asymptomatic PHPT have been carried out on the field, with inconsistent results, even when the same assessment tools were used [10,14,15]. Data from the trials of Rao et al. [10]. and Ambrogini et al. [14] reported a benefit from surgery for the emotional role function scores, as assessed by the ShortForm-36 general health survey questionnaire (TABLE 1). Conversely, Bollerslev et al. reported no significant difference in the same quality of life scores in a total of 191 patients with asymptomatic PHPT randomized to surgery versus medical observation (TABLE 1) [15]. On the other hand, discordance between the results on psychological and cognition assessment before and after surgery is also reported [6–10,14–16]. The heterogeneity of the results, as observed for other nonclassical complications of PHPT, is mostly due to the lack of homogeneity of the patients studied, as well as of the appropriate control groups, different methodologies and different time of observation and follow-up, small sample size and the inclusion of symptomatic patients in some cases. The link between PHPT and neurocognitive function remains unclear. The biochemical perturbations of the parathyroid axis have been questioned as hypercalcemia is well known to be associated with changes in the concentration of cerebrospinal fluid, thus impacting the brain functions [22,23]. A recent study from our group tested the hypothesis of a direct effect of hypercalcemia in many forms of activity-dependent synaptic plasticity [24]. The mechanisms associated with synaptic plasticity indeed require the mobilization of ionized calcium at preand postsynaptic level, thus increasing the ion release and its effect on the N-methyl D-aspartate receptor [24–27]. Hence, the Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)

Quality of life in patients with PHPT

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Table 2. Neuropsychological manifestations in patients with primary hyperparathyroidism before surgery. Study (year)

Study design

Patients (n)

Numann et al. (1984)

Case–control study

10

Yu et al. (2011)

Historical, prospective cohort study

1424

Disease severity

Mild

Tools

Result

Wechsler Logical Memory and Associate Learning; Wechsler Memory Digit Span, Similarities subtest of the Wechsler Adult Intelligence Scales

17% reduction in Wechsler Memory Quotient

[34]

General Registration Office; Cancer Registry Data; Scottish Care Information-Diabetes Collaboration data; and Scottish Morbidity Records 01; Tayside community prescription data

Hazard ratio for psychiatric disease: 2.38

[35]

high extracellular calcium concentration could exert a negative effect on neuronal function and synaptic plasticity. [24]. By using the repetitive transcranial magnetic stimulation at 5 Hz, our results demonstrated that chronic and acute hypercalcemia significantly affect short-term synaptic plasticity [24]. Moreover, there was significantly less increase of some parameters evoked during the transcranial stimulation (the motor-evoked potential) in patients with chronic hypercalcemia compared with healthy subjects [24]. These findings suggested that ionized calcium could modulate neurotransmission by altering short-term synaptic plasticity, possibly by acting on N-methyl D-aspartate receptors or depressing Na+ current [24]. Other studies investigated the mechanisms associated with the neuropsychological involvement in PHPT from a clinical point of view [8,11,17]. Results from the Rotterdam study showed an association between high serum calcium and worse cognitive performance, both in the global and in the specific domain [28]. A recent one showed a correlation between serum calcium and the severity of some depressive scores, suicidal ideation and mental health scores [11]. Nevertheless, while these results are consistent with other reports in literature, other authors described different findings [8,17]. Among the other factors hypothesized as possibly influencing the higher rate of mood disorders and cognitive dysfunction in PHPT patients, parathyroid hormone (PTH) has been investigated. The presence of a member of the PTH receptor superfamily (PTH 2 receptor) in different areas of the CNS and of the tuberoinfundibular peptide of 39 residues in the bovine hypothalamus [29] has indeed raised the hypothesis of an influence of PTH on brain functions. Although the potential role of PTH receptor in the brain structures is not yet defined, other studies investigated the relationship between serum PTH and neuropsychological function [7,8,30]. In particular, a reduced score in both cognitive and psychological tests was found in some, but not all the studies, as well as a significant association with change in PTH and both psychological and cognitive function change [7,8,30]. In order to best define the mechanisms leading to central disorders in PHPT, the evaluation of cerebral blood flow has also been carried out in two small studies by using singlephoton emission computed tomography [31,32]. Cermik et al. www.expert-reviews.com

Ref.

reported a hypoperfusion of the brain cortex at different levels in PHPT patients, with a significant correlation between the vascular findings and serum calcium and PTH levels [31]. Results from Mjaland et al. study are in line with these data and also reported a significant improvement of the cerebral blood flow, as well as of depression scores, after surgery [32]. As for other topics previously discussed, the studies investigating the possible mechanism linking PHPT and CNS disorders are not conclusive. They substantially differ for the design, the population studied and the time of follow-up, as well as for the difficulty of completely distinguishing between the possible role of calcium and/or PTH changes and the interrelationship between biochemical markers and vascular abnormalities on such multifactorial disorders. Further investigations of the possible role of calcium and PTH (whose effect on vasoconstriction on peripheral circulation has been reported) on cerebral blood flow perturbation in PHPT are therefore warranted. Recent literature

Studies on quality of life in PHPT can be dated back from 30 years ago and have been aimed to better define the presence, type and possible reversibility of neuropsychological symptoms associated with the disease (TABLE 2) [6–20,33,34]. The present section is aimed to review the most important and recent data from literature on the field. After the only three randomized controlled trials published between 2004 and 2007 [10,14,15], many studies focused on the prevalence of neuropsychiatric symptoms and particularly on the effect of surgery [6–20]. These are mostly observational studies of different size, which used different tests and scores and observed patients undergoing surgery at different time points (TABLE 3). Moreover, many of these studies compared patients undergoing parathyroid surgery to patients with other endocrine disorders. One of the most recent one is a prospective multicenter study reporting data on depression, anxiety, suicidal ideation and health-related quality of life in patients with PHPT evaluated pre- and postsurgery and compared with a control group of patients with nontoxic thyroid nodules [11]. The study included 194 patients with PHPT and 186 control subjects from nine German hospitals. The authors reported 115

116

Prospective study (follow-up 1 year)

Prospective, multicenter study (follow-up to 12 months)

Prospective, case–control study (mean surgeryretest interval of 3 months)

Prospective, case–control study (follow-up to 1 month)

Prospective, case–control study (follow-up to 6 months)

Joborn et al. (1989)

Pasieka et al. (2002)

Chiang et al. (2005)

Roman et al. (2005)

Walker et al. (2009)

Symptomatic PHPT

Symptomatic PHPT

Symptomatic PHPT

41% of PHPT patients were asymptomatic

Asymptomatic PHPT

125

20

41 pre- and postoperatively

39

Disease severity

30

Patients (n)

[13]

[16]

[7]

[6]

Preoperatively: no significant difference in the scores between PHPT patients versus controls Postoperatively: no improvement between pre- and postoperative measures in PHPT patients; no significant difference in the scores between PHPT patients versus controls Preoperatively: higher BDI scores in PHPT patients than controls Postoperatively: all the scores improve in PHPT and control groups Preoperatively: worse scores for depression, state anxiety, trait anxiety, immediate and delayed recall of contextually related material, immediate word list recall, nonverbal abstraction Postoperatively: improvement in depressive symptoms, trait anxiety, immediate and delayed recall of contextually related material, nonverbal abstraction, visual concentration and attention

Tests of attentional flexibility (Stroop test, Digit symbol test of the Wechsler Adult Intelligence Scale-Revised); two memory tests for prose and nonverbal material; Eight State Questionnaire; Speilberger STAI; BDI BDI; Spielberger STAI; RAVLT; GMLT

BDI; STAI-Y; Wechsler Memory Scale Logical Memory Test, Russell revision; Buschke Selective Reminding Test; Rey Visual Design Learning Test; Booklet Category Test, Victoria revision; Rosen Target Detection Test

Visual analog scale; QOL uniscale; self-rated health uniscale; patient satisfaction score; general health assessment score

HSC

Postoperatively: parathyroidectomy assessment of symptoms score significantly decreased

Ref. [33]

Result Preoperatively: highest HSC values for PHPT patients Postoperatively: significant improvement in the HSC scores

Tools

BDI: Beck Depression Inventory; GMLT: Groton Maze Learning Test; HADS: Hospital Anxiety and Depression scale; HSC: Hopkins Symptom Checklist; PHPT: Primary hyperparathyroidism; PHQ-9: Patient Health Questionnaire–9; RAVLT: Rey Auditory Verbal Learning Test; SF-36: 36-item ShortForm health survey; STAI: State-Trait Anxiety Inventory.

Study design

Study (year)

Table 3. Neuropsychological manifestations in patients with primary hyperparathyroidism before and/or after parathyroid surgery.

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Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)

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Cross-sectional (mean time followup 7.4 [range 5–15] years)

Prospective, cohort study (follow-up to 6 months)

Prospective randomized trial (surgery vs observation) (follow-up to 6 months)

Prospective study

Prospective, case–control study (follow-up 3 months)

Amstrup et al. (2011)

Roman et al. (2011)

Perrier et al. (2009)

Benge et al. (2009)

Kahal et al. (2012)

HADS; Mood Rating Scale

24

Asymptomatic PHPT

Indices investigating cognition, memory and depression

111 preoperatively; 68 postoperatively

Functional MRI of the brain, sleep assessment, and validated neuropsychological battery

18

Asymptomatic PHPT

BDI; STAI; Brief Symptom Inventory-18; RAVLT; GMLT

212

Tools Health-related quality of life 36-Item Short Form (SF-36 Danish version 2); WHO-Five Well-being Index questionnaire on general well-being and illnesses

Disease severity

51

Patients (n)

[19]

[18]

Postoperatively: decrease in hypersomnolence at 6 weeks after surgery versus observation group

Preoperatively: cognitive slowing, reduction in psychomotor speed, memory impairment, depression Postoperatively: trend for improvement on timed tests, information processing speed, depression and decline in memory

[17]

[8]

Preoperatively: BDI indicative of mild depression; STAI indicative of clinically significant anxiety; RAVLT and GMLT scores within normal limits; Postoperatively: significant improvement of all scores, but except trait anxiety scores

Preoperatively: higher average score on HADS-D (depression) for PHPT; Postoperatively: improvement in any score

[12]

Ref.

Postoperatively: lower scores in physical functioning, role limitation caused by emotional problems, vitality, mental component and general health in PHPT patients versus controls

Result

BDI: Beck Depression Inventory; GMLT: Groton Maze Learning Test; HADS: Hospital Anxiety and Depression scale; HSC: Hopkins Symptom Checklist; PHPT: Primary hyperparathyroidism; PHQ-9: Patient Health Questionnaire–9; RAVLT: Rey Auditory Verbal Learning Test; SF-36: 36-item ShortForm health survey; STAI: State-Trait Anxiety Inventory.

Study design

Study (year)

Table 3. Neuropsychological manifestations in patients with primary hyperparathyroidism before and/or after parathyroid surgery (cont.).

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Quality of life in patients with PHPT

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118

194 Prospective, multicenter, case–control study Weber et al. (2013)

BDI: Beck Depression Inventory; GMLT: Groton Maze Learning Test; HADS: Hospital Anxiety and Depression scale; HSC: Hopkins Symptom Checklist; PHPT: Primary hyperparathyroidism; PHQ-9: Patient Health Questionnaire–9; RAVLT: Rey Auditory Verbal Learning Test; SF-36: 36-item ShortForm health survey; STAI: State-Trait Anxiety Inventory.

[11]

Preoperatively: elevated mean HADS anxiety and PHQ-9 scores, reduced SF-36 score Postoperatively: anxiety and PHQ-9 scores declined steadily; SF-36 scores improved HADS, PHQ-9, SF-36

[20]

Preoperatively: impaired concentration, decreased nonverbal learning process, difficulties in using direct memory, verbal fluency and visual constructive abilities Postoperatively: improvement in visual memory, visualconstructive abilities and direct memory Benton Visual Retention Test, Wisconsin Card Sorting Test, Memory Verbal Learning Test, RAVLT, Trail Making Test A & B, Verbal Fluency Test, Beck Depression Inventory Asymptomatic PHPT Prospective, case–control study Babin´ska et al. (2012)

35

Ref. Result Tools Disease severity Study design

Patients (n)

Cipriani, Romagnoli, Cilli, Piemonte, Pepe & Minisola

Study (year)

Table 3. Neuropsychological manifestations in patients with primary hyperparathyroidism before and/or after parathyroid surgery (cont.).

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higher scores preoperatively for PHPT patients compared with both the control group of thyroid patients and healthy population as far as anxiety and depressive questionnaires are concerned [11]. Moreover, 33% of PHPT patients presented mild or moderate symptoms and 19.6% severe symptoms compared with 17.7 and 9.1% in the thyroid patients [11]. PHPT patients showed significantly lower Short Form-36 general health survey physical and mental health summary scores than control groups and healthy subjects [11]. A significant increase of the above-mentioned scores 6 and 12 months after surgery is reported [11]. Suicidal ideation was present in 22% of PHPT and 11.4% of thyroid patients before surgery, with a significant decrease up to 10.7% postoperatively in PHPT patients [11]. A nice correlation between serum calcium, and not PTH levels, and depression scores and degree of suicidal ideation was found [11]. Consistent results were reported by Espiritu et al., which observed a 63.5% decrease of depression score at 1 month and 65.6% at 1 year from surgery [9]. The improvement in depression scores after parathyroidectomy was greater than after thyroidectomy in the control group [9]. Additionally, there was a significant decline in depression scores in surgical versus observed PHPT patients with scores of 10 or greater at all time points [9]. A similar decline was observed for scores investigating major life events and quality of life [9]. Finally, serum calcium and PTH levels correlated with depression scores, patients with serum calcium above 11 mg/dl showing higher values of the depressive indexes [9]. The evaluation of quality of life has been performed in another recent small study involving 51 former PHPT patients [12]. The Short Form-36 general health survey and the WHO-Five Wellbeing scale were used. Former PHPT patients (mean followup time from surgery: 7.4) still showed significant lower values as far as mental component parameters are concerned compared with 51 healthy age-matched controls [12]. The results were adjusted for age, BMI and the presence of cardiovascular disease, as obesity and cardiovascular disease represent one of the most frequent chronic diseases associated with PHPT [12]. Quality of life has been evaluated recently in studies investigating both mood disorders and cognitive functions [6,8,34]. Walker et al. evaluated the estimated intellectual quotient, the memory for contextually related material, the word list and visual memory, nonverbal abstraction, visual concentration/attention, auditory attention, mental manipulation, as well as depression in a case–control study assessing 39 postmenopausal women with mild PHPT before and 6 months after surgery [6]. The study reported a reduced performance in verbal memory and nonverbal abstraction domains, as well as higher frequency of depressive and anxious symptoms in PHPT patients, compared with 89 postmenopausal controls, without any interrelation between cognitive and psychological symptoms [6]. Some of the psychiatric and cognitive deficits significantly improved when patients were evaluated 6 months after parathyroidectomy [6]. Expert Rev. Pharmacoecon. Outcomes Res. 14(1), (2014)

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Quality of life in patients with PHPT

Roman et al. reported a postoperative improvement (6-month follow-up) in neurocognitive scores, particularly visuospatial working memory, as well as in depression and anxiety scores in PHPT patients [8]. The postoperative reduction in serum PTH was significantly associated, in a bivariate analysis, with a decrease in anxiety scores and in turn associated with an improvement in visuospatial working memory [8]. Inconsistent results were reported in the study by Benge et al., which did not include a control group and evaluated 111 PHPT patients at baseline, showing a cognitive slowing, reduction in psychomotor speed, memory and depression. Depression and information processing speed improved after surgery (68 patients being operated), while verbal memory declined the last particularly among older patients [18]. The study by Perrier et al. is a small prospective randomized controlled trial comparing parathyroidectomy and observation as far as parameters evaluating cognition in asymptomatic PHPT are concerned [19]. Functional MRI (fMRI) of the brain, sleep assessment and neuropsychological tests were performed at baseline, 6 weeks and 6 months after parathyroidectomy [19]. The authors described a significant association between sleepiness and brain function, assessed by fMRI, a decrease in daytime sleepiness in surgery-treated patients, compared with observation at 6 weeks, but not at 6 months [19]. Total sleep time was not different between the two groups and it correlated with PTH levels at both 6 weeks and 6 months [19]. No differences were found between the two groups as far as cognitive changes are concerned [19]. Changes in PTH serum levels were associated with changes in voxel activity in the left precentral gyrus at fMRI [19]. Different tools and different follow-up time were employed in the recent Babin´ska et al. study [20]. The authors reported a reduction in concentration, nonverbal learning processes, direct memory, verbal fluency and visualconstructive abilities in 35 patients with mild PHPT compared with control subjects and no correlation between neurocognitive scores and biochemical markers [20]. Visual memory, visual-constructive abilities and direct memory significantly increased 1 year after surgery [20]. Finally, Yu et al. recently performed a historical, prospective and population-based study that aimed to determine the risk of mortality and morbidities in mild PHPT patients in a Scottish region between 1997 and 2006 [35]. Each PHPT patient was matched with five population-based

Review

comparators selected from the general population. Among the diagnoses evaluated, the authors reported in PHPT patients an increased risk of psychiatric disease whose nature was not clarified [35]. Expert commentary

Despite the great amount of evidences on the neuropsychological manifestations in PHPT patients, the 2008 Workshop on Asymptomatic PHPT concluded that studies on the field do not allow a definite conclusion on the benefit of surgery versus observation [1]. Actually, those aspects of the disease are still debated and need further investigation, both concerning the prevalence and the possible effect of surgery. As for the experts’ conclusions, neuropsychological complications cannot be included in the criteria for parathyroidectomy and further randomized trials investigating the effect of surgery versus observation in asymptomatic PHPT and the possible mechanisms related to the neuropsychiatric PHPT-associated disease should be designed. However, the possibility of a placebo effect of surgery on psychiatric manifestations, well-being sense and quality of life and the presence of other factors hardly to define in any given patient, as those related to lifestyle, socioeconomic aspects and the burden of being diagnosed with a disease, should be taken into account in designing those studies, as well as in patients’ clinical evaluation. Five-year view

Many aspects of the above-mentioned study’ findings, particularly those related to the benefit of parathyroidectomy, are still inconsistent. Further data are therefore needed to define the neuropsychological and cognitive deficits specifically associated with PHPT [36]. Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Key issues .

The overall recent available evidence further characterize the nature of the neuropsychiatric, even subclinical, symptoms associated with PHPT and their effect on quality of life.

.

Additionally, some data support the hypothesis of a beneficial effect of parathyroidectomy on quality of life and psychological functioning, even if different domains of both cognition and metal status showed an improvement in the different reports.

.

Primary hyperparathyroidism therefore appears to be an endocrine disorder with multiorgan complications, whose definition and management are definitely warranted.

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hyperparathyroidism have a reduced quality of life compared with population–based healthy sex, age and season-matched controls. Eur J Endocrinol 2011;165(5): 753-60

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Quality of life in patients with primary hyperparathyroidism.

The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed th...
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